Technetium-99m has become widely used in the field of nuclear medicine for the scanning and visualizing of various organs and tissues in the body. When coupled with various substances it has been used, for example, for visualization of the brain, lungs, blood pool, thyroid, liver, spleen, bone and kidney. One of the reasons for the wide-spread acceptance of technetium-99m in the field of nuclear medicine is its relatively short half-life of about 6 hours. While the short half-life of technetium-99m is advantageous in minimizing the physiological risks associated with the use of radioisotopes, it also makes it highly desirable to generate the short-lived radionuclide as close to its time of use as possible.
The patent literature provides many examples of apparatus and methods which can be used for the generation of technetium-99m (referred to in the generator art as the "daughter radionuclide") from molybdenum-99 (referred to in the generator art as the "parent radionuclide"); see, for example, U.S. Pat. Nos. 3,369,121 and 3,920,995. The generators currently in use for the generation of technetium-99m from molybdenum-99 comprise a containerized support medium, e.g., chromatographic grade alumina, having adsorbed thereon molybdenum-99. The container is part of a sterile system which further comprises inlet means for introducing an eluant onto the support medium having the molybdenum-99 adsorbed thereon, and outlet means for removing the eluate containing the technetium-99m from the support medium. The operation of this type of generator, as explained by Boyd, "Recent Developments in Generators of .sup.99m Tc", Proceedings of a Symposium on Radiopharmaceuticals and Labelled Compounds, Copenhagen, Mar. 26-30, l973, International Atomic Energy Agency, Vienna (1973), is based on the differences in the distribution-coefficient values of the carrier material for the ions of molybdenum-99 and technetium-99m. The passage of the proper eluant through the support medium will result in the elution of technetium-99m. If physiological saline is utilized as the eluant, the technetium-99m will be eluted in the form of sodium pertechnetate. The pertechnetate ion has as valence of +7, and is technetium's highest and most stable oxidation state in solution.
Commercial generators of the above-described type, having alumina as the support medium, are delivered to customers for periodic elution. The amount (in millicuries) of technetium-99m obtained in the initial elution will depend on the original potency of the generator. The activity obtained in subsequent elutions will depend on the time interval between elutions. A problem often encountered with the generators is low yield (incomplete removal) of technetium-99m. These yield problems occur most frequently during the early elutions of high activity generators, and are usually the result of a delayed release of technetium-99m from the alumina. It is possible for the generator user to compensate for the low yield by an additional elution of the generator, but such an additional elution is highly undesirable because of the additional risk of exposure to radiation and because of the inconvenience involved.
Low yield problems have been discussed in the literature (see Boyd, supra. and Vesely et al. "Some Chemical and Analytical Problems Connected with Tc-99m Generators," Radiopharmaceuticals from Generator-Produced Radionuclides (Proc. Panel Vienna, 1970) International Atomic Energy Agency, Vienna (1970)) and have been attributed to the effect of ionizing radiation on the valance state of technetium-99m. The reductive nature of the combination of high radiation levels and water may cause technetium to go from its highest valence state of +7 to lower oxidation states, making the technetium difficult, if not impossible, to remove from the generator system with isotonic saline solution.
The prior art has dealt with the problem of low yields by using on oxidizing agent in the saline eluant or on the alumina column (see, for example, U.S. Pat. No. 3,664,964). The major disadvantage of this technique is that the technetium eluate from the generator is frequently used, as described above, to label substances for localization (and subsequent imaging and visualization) in various organs and tissues. The materials are often in the form of commercial kits which contain, in addition to the substance to be labelled, a reducing agent to facilitate labelling. The presence of an oxidizing agent in the eluate can be detrimental to this process.